Shunt placement through the sclera

ABSTRACT

The present invention generally relates to intraocular shunts, and in particular, to intraocular shunts configured to form a drainage pathway between the anterior chamber and the intra-Tenon&#39;s space.

FIELD OF THE INVENTION

The present invention generally relates to devices for reducingintraocular pressure by creating a drainage pathway between the anteriorchamber of the eye and the intra-Tenon's space.

BACKGROUND

Glaucoma is a disease in which the optic nerve is damaged, leading toprogressive, irreversible loss of vision. It is typically associatedwith increased pressure of the fluid (i.e., aqueous humor) in the eye.Untreated glaucoma leads to permanent damage of the optic nerve andresultant visual field loss, which can progress to blindness. Once lost,this damaged visual field cannot be recovered. Glaucoma affects 1 in 200people aged fifty and younger, and 1 in 10 over the age of eighty for atotal of approximately 70 million people worldwide, and glaucoma is thesecond leading cause of blindness in the world.

The importance of lowering intraocular pressure (IOP) in delayingglaucomatous progression has been well documented. When drug therapyfails, or is not tolerated, surgical intervention is warranted. Surgicalfiltration methods for lowering intraocular pressure by creating a fluidflow-path between the anterior chamber and the subconjunctival tissuehave been described. One particular ab interno glaucoma filtrationmethod has been described whereby an intraocular shunt is implanted bydirecting a needle which holds the shunt through the cornea, across theanterior chamber, and through the trabecular meshwork and sclera, andinto the subconjunctival space. See, for example, U.S. Pat. No.6,544,249, U.S. patent application publication number 2008/0108933, andU.S. Pat. No. 6,007,511.

Proper positioning of a shunt in the subconjunctival space is criticalin determining the success or failure of subconjunctival glaucomafiltration surgery for a number of reasons. In particular, the locationof the shunt has been shown to play a role in stimulating the formationof active drainage structures such as veins or lymph vessels. See, forexample, U.S. patent application publication number 2008/0108933. Inaddition, it has been suggested that the conjunctiva itself plays acritical role in glaucoma filtration surgery. A healthy conjunctivaallows drainage channels to form and less opportunity for inflammationand scar tissue formation, which are frequent causes of failure insubconjunctival filtration surgery. See, for example, Yu et al.,Progress in Retinal and Eye Research, 28: 303-328 (2009).

SUMMARY

The present invention provides intraocular shunts that are designed toavoid contact with the conjunctiva when deployed into thesubconjunctival space. In particular, the present invention providesintraocular shunts that are configured to form a drainage pathwaybetween the anterior chamber of the eye and the intra-Tenon's space.Design of an intraocular shunt such that the shunt inlet (i.e., theportion of the shunt that receives fluid from an anterior chamber of theeye) terminates in the anterior chamber and the shunt outlet (i.e., theportion of the shunt that directs fluid to the intra-Tenon's space)terminates in the intra-Tenon's space safeguards the integrity of theconjunctiva to allow subconjunctival drainage pathways to successfullyform.

The intraocular shunts of the invention define a hollow body comprisingan inlet and an outlet, and the hollow body is configured to form apassage from the anterior chamber of the eye to the intra-Tenon's space.In particular, the hollow body has a length sufficient to provide apassageway between the anterior chamber and the intra-Tenon's space.

In certain aspects, the invention generally provides shunts composed ofa material that has an elasticity modulus that is compatible with anelasticity modulus of tissue surrounding the shunt. In this manner,shunts of the invention are flexibility matched with the surroundingtissue, and thus will remain in place after implantation without theneed for any type of anchor that interacts with the surrounding tissue.Consequently, shunts of the invention will maintain fluid flow away foran anterior chamber of the eye after implantation without causingirritation or inflammation to the tissue surrounding the eye.

In other aspects, the invention generally provides shunts in which aportion of the shunt is composed of a flexible material that is reactiveto pressure, i.e., an inner diameter of the shunt fluctuates dependingupon the pressures exerted on that portion of the shunt. Thus, theflexible portion of the shunt acts as a valve that regulates fluid flowthrough the shunt. After implantation, intraocular shunts have pressureexerted upon them by tissues surrounding the shunt (e.g., scleraltissue) and pressure exerted upon them by aqueous humor flowing throughthe shunt. When the pressure exerted on the flexible portion of theshunt by the surrounding tissue is greater than the pressure exerted onthe flexible portion of the shunt by the fluid flowing through theshunt, the flexible portion decreases in diameter, restricting flowthrough the shunt. The restricted flow results in aqueous humor leavingthe anterior chamber at a reduced rate.

When the pressure exerted on the flexible portion of the shunt by thefluid flowing through the shunt is greater than the pressure exerted onthe flexible portion of the shunt by the surrounding tissue, theflexible portion increases in diameter, increasing flow through theshunt. The increased flow results in aqueous humor leaving the anteriorchamber at an increased rate.

The flexible portion of the shunt may be any portion of the shunt. Incertain embodiments, the flexible portion is a distal portion of theshunt. In certain embodiments, the entire shunt is composed of theflexible material.

Other aspects of the invention generally provide multi-port shunts. Suchshunts reduce probability of the shunt clogging after implantationbecause fluid can enter or exit the shunt even if one or more ports ofthe shunt become clogged with particulate. In certain embodiments, theshunt includes a hollow body defining a flow path and more than twoports, in which the body is configured such that a proximal portionreceives fluid from the anterior chamber of an eye and a distal portiondirects the fluid to a location of lower pressure with respect to theanterior chamber.

The shunt may have many different configurations. In certainembodiments, the proximal portion of the shunt (i.e., the portiondisposed within the anterior chamber of the eye) includes more than oneport and the distal portion of the shunt (i.e., the portion that islocated in the intra-Tenon's space) includes a single port. In otherembodiments, the proximal portion includes a single port and the distalportion includes more than one port. In still other embodiments, theproximal and the distal portions include more than one port.

The ports may be positioned in various different orientations and alongvarious different portions of the shunt. In certain embodiments, atleast one of the ports is oriented at an angle to the length of thebody. In certain embodiments, at least one of the ports is oriented 90°to the length of the body.

The ports may have the same or different inner diameters. In certainembodiments, at least one of the ports has an inner diameter that isdifferent from the inner diameters of the other ports.

Other aspects of the invention generally provide shunts with overflowports. Those shunts are configured such that the overflow port remainsclosed until there is a pressure build-up within the shunt sufficient toforce open the overflow port. Such pressure build-up typically resultsfrom particulate partially or fully clogging an entry or an exit port ofthe shunt. Such shunts reduce probability of the shunt clogging afterimplantation because fluid can enter or exit the shunt by the overflowport even in one port of the shunt becomes clogged with particulate.

In certain embodiments, the shunt includes a hollow body defining aninlet configured to receive fluid from an anterior chamber of the eyeand an outlet configured to direct the fluid to a location of lowerpressure with respect to the anterior chamber, the body furtherincluding at least one slit. The slit may be located at any place alongthe body of the shunt. In certain embodiments, the slit is located inproximity to the inlet. In other embodiments, the slit is located inproximity to the outlet. In certain embodiments, there is a slit inproximity to both the inlet and the outlet of the shunt.

In certain embodiments, the slit has a width that is substantially thesame or less than an inner diameter of the inlet. In other embodiments,the slit has a width that is substantially the same or less than aninner diameter of the outlet. Generally, the slit does not direct thefluid unless the outlet is obstructed. However, the shunt may beconfigured such that the slit does direct at least some of the fluideven if the inlet or outlet is not obstructed.

In other aspects, the invention generally provides a shunt having avariable inner diameter. In particular embodiments, the diameterincreases from inlet to outlet of the shunt. By having a variable innerdiameter that increases from inlet to outlet, a pressure gradient isproduced and particulate that may otherwise clog the inlet of the shuntis forced through the inlet due to the pressure gradient. Further, theparticulate will flow out of the shunt because the diameter onlyincreases after the inlet.

In certain embodiments, the shunt includes a hollow body defining a flowpath and having an inlet configured to receive fluid from an anteriorchamber of an eye and an outlet configured to direct the fluid to theintra-Tenon's space, in which the body further includes a variable innerdiameter that increases along the length of the body from the inlet tothe outlet. In certain embodiments, the inner diameter continuouslyincreases along the length of the body. In other embodiments, the innerdiameter remains constant along portions of the length of the body. Theshunts discussed above and herein are described relative to the eye and,more particularly, in the context of treating glaucoma and solving theabove identified problems relating to intraocular shunts. Nonetheless,it will be appreciated that shunts described herein may find applicationin any treatment of a body organ requiring drainage of a fluid from theorgan and are not limited to the eye.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a cross-sectional diagram of the general anatomy of theeye.

FIG. 2 provides another cross-sectional view the eye, and certainanatomical structures of the eye.

FIG. 3 depicts, implantation of an intraocular shunt with a distal endof a deployment device holding a shunt, shown in cross-section.

FIG. 4 depicts an example of a hollow shaft configured to hold anintraocular shunt.

FIG. 5A depicts a hollow shaft having a bend in a distal portion of theshaft. FIG. 5B depicts a hollow shaft having a U-shape. FIG. 5C depictsa hollow shaft having a V-shape.

FIG. 6A depicts a simulation of the exit site distance from the limbusand height above the iris after needle entry at the limbus using an abinterno procedure. FIG. 6B depicts a simulation of the exit sitedistance from the limbus and height above the iris after needle entryabove the limbus using an ab interno procedure.

FIG. 7A depicts the tip bevel portion of a triple-ground needle tip.FIG. 7B depicts the flat bevel portion of a triple-ground needle tip.FIG. 7C depicts an intraocular shunt within a triple-ground needle tip.FIG. 7D depicts 100% penetration of the flat bevel portion of atriple-ground needle tip through the sclera of an eye.

FIG. 8A depicts an intraocular shunt inserted into the scleral channelusing a beveled needle tip to completely penetrate the scleral tissueprior to insertion of the shunt. FIG. 8B depicts an intraocular shuntinserted into the scleral channel using a beveled needle tip topartially penetrate the scleral tissue prior to insertion of the shunt.

FIG. 9 provides a schematic of a shunt having a flexible portion.

FIGS. 10A, 10B and 10C provide schematics of a shunt implanted into aneye for regulation of fluid flow from the anterior chamber of the eye toa drainage structure of the eye.

FIG. 11 shows different embodiments of multi-port shunts. FIG. 11A showsan embodiment of a shunt in which the proximal portion of the shuntincludes more than one port and the distal portion of the shunt includesa single port. FIG. 11B shows another embodiment of a shunt in which theproximal portion includes a single port and the distal portion includesmore than one port. FIG. 11C shows another embodiment of a shunt inwhich the proximal portions include more than one port and the distalportions include more than one port.

FIGS. 12A and 12B show different embodiments of multi-port shunts havingdifferent diameter ports.

FIGS. 13A, 13B and 13C provide schematics of shunts having a slitlocated along a portion of the length of the shunt.

FIG. 14 depicts a shunt having multiple slits along a length of theshunt.

FIG. 15 depicts a shunt having a slit at a proximal end of the shunt.

FIG. 16 provides a schematic of a shunt that has a variable innerdiameter.

FIG. 17 is a schematic showing an embodiment of a shunt deploymentdevice according to the invention

FIG. 18 shows an exploded view of the device shown in FIG. 1.

FIGS. 19A to 19D are schematics showing different enlarged views of thedeployment mechanism of the deployment device.

FIGS. 20A to 20C are schematics showing interaction of the deploymentmechanism with a portion of the housing of the deployment device.

FIG. 21 shows a cross sectional view of the deployment mechanism of thedeployment device.

FIGS. 22A and 22B show schematics of the deployment mechanism in apre-deployment configuration. FIG. 22C shows an enlarged view of thedistal portion of the deployment device of FIG. 22A. This figure showsan intraocular shunt loaded within a hollow shaft of the deploymentdevice.

FIGS. 23A and 23B show schematics of the deployment mechanism at the endof the first stage of deployment of the shunt from the deploymentdevice. FIG. 23C shows an enlarged view of the distal portion of thedeployment device of FIG. 23A. This figure shows an intraocular shuntpartially deployed from within a hollow shaft of the deployment device.

FIG. 24A shows a schematic of the deployment device after deployment ofthe shunt from the device. FIG. 24B show a schematic of the deploymentmechanism at the end of the second stage of deployment of the shunt fromthe deployment device. FIG. 24C shows an enlarged view of the distalportion of the deployment device after retraction of the shaft with thepusher abutting the shunt. FIG. 24D shows an enlarged view of the distalportion of the deployment device after deployment of the shunt.

FIGS. 25 and 26 show an intraocular shunt deployed within the eye. Aproximal portion of the shunt resides in the anterior chamber and adistal portion of the shunt resides within the intra-Tenon's space. Amiddle portion of the shunt resides in the sclera.

DETAILED DESCRIPTION

FIG. 1 provides a schematic diagram of the general anatomy of the eye.An anterior aspect of the anterior chamber 1 of the eye is the cornea 2,and a posterior aspect of the anterior chamber 1 of the eye is the iris4. Beneath the iris 4 is the lens 5. The anterior chamber 1 is filledwith aqueous humor 3. The aqueous humor 3 drains into a space(s) 6 belowthe conjunctiva 7 through the trabecular meshwork (not shown in detail)of the sclera 8. The aqueous humor is drained from the space(s) 6 belowthe conjunctiva 7 through a venous drainage system (not shown).

FIG. 2 provides a cross-sectional view of a portion of the eye, andprovides greater detail regarding certain anatomical structures of theeye. In particular, FIG. 2 shows the relationship of the conjunctiva 12and Tenon's capsule 13. Tenon's capsule 13 is a fascial layer ofconnective tissue surrounding the globe and extra-ocular muscles. Asshown in FIG. 2, it is attached anteriorly to the limbus of the eye andextends posteriorly over the surface of the globe until it fuses withthe dura surrounding the optic nerve. In FIG. 2, number 9 denotes thelimbal fusion of the conjunctiva 12 and Tenon's capsule 13 to the sclera11. The conjunctiva 12 and Tenon's capsule 13 are separate membranesthat start at the limbal fusion 9 and connect to tissue at the posteriorof the eye. The space formed below the conjunctiva 12 is referred to asthe subconjunctival space, denoted as number 14. Below Tenon's capsule13 there are Tenon's adhesions that connect the Tenon's capsule 13 tothe sclera 11. The space between Tenon's capsule 13 and the sclera 11where the Tenon's adhesions connect the Tenon's capsule 13 to the sclera11 is referred to as the intra-Tenon's space, denoted as number 10.

In conditions of glaucoma, the pressure of the aqueous humor in the eye(anterior chamber) increases and this resultant increase of pressure cancause damage to the vascular system at the back of the eye andespecially to the optic nerve. The treatment of glaucoma and otherdiseases that lead to elevated pressure in the anterior chamber involvesrelieving pressure within the anterior chamber to a normal level.

Glaucoma filtration surgery is a surgical procedure typically used totreat glaucoma. The procedure involves placing a shunt in the eye torelieve intraocular pressure by creating a pathway for draining aqueoushumor from the anterior chamber of the eye. The shunt is typicallypositioned in the eye such that it creates a drainage pathway betweenthe anterior chamber of the eye and a region of lower pressure. Variousstructures and/or regions of the eye having lower pressure that havebeen targeted for aqueous humor drainage include Schlemm's canal, thesubconjunctival space, the episcleral vein, the suprachoroidal space, orthe subarachnoid space. Methods of implanting intraocular shunts areknown in the art. Shunts may be implanted using an ab externo approach(entering through the conjunctiva and inwards through the sclera) or anab interno approach (entering through the cornea, across the anteriorchamber, through the trabecular meshwork and sclera).

Ab interno approaches for implanting an intraocular shunt in thesubconjunctival space are shown for example in Yu et al. (U.S. Pat. No.6,544,249 and U.S. patent publication number 2008/0108933) and Prywes(U.S. Pat. No. 6,007,511), the contents of each of which areincorporated by reference herein in its entirety. Briefly and withreference to FIG. 3, a surgical intervention to implant the shuntinvolves inserting into the eye a deployment device 15 that holds anintraocular shunt, and deploying the shunt within the eye 16. Adeployment device 15 holding the shunt enters the eye 16 through thecornea 17 (ab interno approach). The deployment device 15 is advancedacross the anterior chamber 20 (as depicted by the broken line) in whatis referred to as a transpupil implant insertion. The deployment device15 is advanced through the sclera 21 until a distal portion of thedevice is in proximity to the subconjunctival space. The shunt is thendeployed from the deployment device, producing a conduit between theanterior chamber and the subconjunctival space to allow aqueous humor todrain through the conjunctival lymphatic system.

While such ab interno subconjunctival filtration procedures have beensuccessful in relieving intraocular pressure, there is a substantialrisk that the intraocular shunt may be deployed too close to theconjunctiva, resulting in irritation and subsequent inflammation and/orscarring of the conjunctiva, which can cause the glaucoma filtrationprocedure to fail (See Yu et al., Progress in Retinal and Eye Research,28: 303-328 (2009)). Additionally, commercially available shunts thatare currently utilized in such procedures are not ideal for ab internosubconjunctival placement due to the length of the shunt (i.e., toolong) and/or the materials used to make the shunt (e.g., gold, polymer,titanium, or stainless steel), and can cause significant irritation tothe tissue surrounding the shunt, as well as the conjunctiva, ifdeployed too close.

The present invention provides intraocular shunts that are designed toform a drainage pathway between the anterior chamber of the eye and theintra-Tenon's space and are suitable for use in an ab interno glaucomafiltration procedure. The present invention further relates to methodsfor deploying an intraocular shunt into an eye such that the shunt formsa passage from the anterior chamber of the eye to the intra-Tenon'sspace. Design and/or deployment of an intraocular shunt such that theinlet terminates in the anterior chamber and the outlet terminates inthe intra-Tenon's space safeguards the integrity of the conjunctiva toallow subconjunctival drainage pathways to successfully form. Theconjunctiva is protected from direct contact with the shunt by Tenon'scapsule. Additionally, drainage into the intra-Tenon's space providesaccess to more lymphatic channels than just the conjunctival lymphaticsystem, such as the episcleral lymphatic network. Moreover, designand/or deployment of an intraocular shunt such that the outletterminates in the intra-Tenon's space avoids having to pierce Tenon'scapsule which can otherwise cause complications during glaucomafiltration surgery due to its tough and fibrous nature.

Methods for Intra-Tenon's Shunt Placement

The methods of the invention involve inserting into the eye a hollowshaft configured to hold the intraocular shunt. In certain embodiments,the hollow shaft is a component of a deployment device that may deploythe intraocular shunt. The shunt is then deployed from the shaft intothe eye such that the shunt forms a passage from the anterior chamber tothe intra-Tenon's space. The hollow shaft is then withdrawn from theeye.

Referring to FIGS. 25 and 26, which show an intraocular shunt placedinto the eye such that the shunt forms a passage for fluid drainage fromthe anterior chamber to the intra-Tenon's space. To place the shuntwithin the eye, a surgical intervention to implant the shunt isperformed that involves inserting into the eye 202 a deployment device200 that holds an intraocular shunt 201, and deploying at least aportion of the shunt 201 within intra-Tenon's space 208, within thesubconjunctival space 209 beneath the conjunctiva 210. In certainembodiments, a hollow shaft 206 of a deployment device 200 holding theshunt 201 enters the eye 202 through the cornea 203 (ab internoapproach). The shaft 206 is advanced across the anterior chamber 204 (asdepicted by the broken line) in what is referred to as a transpupilimplant insertion. The shaft 206 is advanced through the sclera 205until a distal portion of the shaft 206 is in proximity to Tenon'scapsule 207. After piercing the sclera 205 with the hollow shaft 206 ofthe deployment device 200, resistance to advancement of the shaft 206encountered by an operator of the deployment device 200 informs theoperator that the shaft 206 has contacted Tenon's capsule 207 and isthus in proximity to Tenon's capsule 207.

Numerous techniques may be employed to ensure that after piercing thesclera 205, the hollow shaft 206 does not pierce Tenon's capsule 207. Incertain embodiments, the methods of the invention involve the use of ahollow shaft 206, in which a portion of the hollow shaft extendslinearly along a longitudinal axis and at least one other portion of theshaft extends off the longitudinal axis. For example, the hollow shaft206 may have a bend in the distal portion of the shaft, a U-shape, or anarcuate or V-shape in at least a portion of the shaft. Examples of suchhollow shafts 206 suitable for use with the methods of the inventioninclude but are not limited to the hollow shafts 206 depicted in FIGS.5A-5C. In embodiments in which the hollow shaft 206 has a bend at adistal portion of the shaft, intra-Tenon's shunt placement can beachieved by using the bent distal portion of the shaft 206 to pushTenon's capsule 207 away from the sclera 205 without penetrating Tenon'scapsule 207. In these embodiments, the tip of the distal end of theshaft 206 does not contact Tenon's capsule 207.

In other embodiments, a straight hollow shaft 206 having a beveled tipis employed. The angle of the beveled tip of the hollow shaft isconfigured such that after piercing the sclera 205, the hollow shaft 206does not pierce Tenon's capsule 207. In these embodiments, the shaft 206is inserted into the eye 202 and through the sclera 205 at an angle suchthat the bevel of the tip is parallel to Tenon's capsule 207, therebypushing Tenon's capsule 207 away from the sclera 205, rather thanpenetrating Tenon's capsule 207, and allowing for deployment of a distalportion of the shunt 201 into the intra-Tenon's space 208.

Once a distal portion of the hollow shaft 206 is within theintra-Tenon's space 208, the shunt 201 is then deployed from the shaft206 of the deployment device 200, producing a conduit between theanterior chamber 204 and the intra-Tenon's space 208 to allow aqueoushumor to drain from the anterior chamber 204 (See FIGS. 25 and 26).

FIG. 4 provides an exemplary schematic of a hollow shaft for use inaccordance with the methods of the invention. This figure shows a hollowshaft 22 that is configured to hold an intraocular shunt 23. The shaftmay hold the shunt within the hollow interior 24 of the shaft, as isshown in FIG. 4. Alternatively, the hollow shaft may hold the shunt onan outer surface 25 of the shaft. In particular embodiments, the shuntis held within the hollow interior of the shaft 24, as is shown in FIG.4. Generally, in one embodiment, the intraocular shunts are of acylindrical shape and have an outside cylindrical wall and a hollowinterior. The shunt may have an inside diameter of approximately 10-250μm, an outside diameter of approximately 190-300 μm, and a length ofapproximately 0.5-20 mm. The hollow shaft 22 is configured to at leasthold a shunt of such shape and such dimensions. However, the hollowshaft 22 may be configured to hold shunts of different shapes anddifferent dimensions than those described above, and the inventionencompasses a shaft 22 that may be configured to hold any shaped ordimensioned intraocular shunt.

Preferably, the methods of the invention are conducted by making anincision in the eye prior to insertion of the deployment device.Although in particular embodiments, the methods of the invention may beconducted without making an incision in the eye prior to insertion ofthe deployment device. In certain embodiments, the shaft that isconnected to the deployment device has a sharpened point or tip. Incertain embodiments, the hollow shaft is a needle. Exemplary needlesthat may be used are commercially available from Terumo Medical Corp.(Elkington, Md). In a particular embodiment, the needle has a hollowinterior and a beveled tip, and the intraocular shunt is held within thehollow interior of the needle. In another particular embodiment, theneedle has a hollow interior and a triple ground point or tip.

The methods of the invention are preferably conducted without needing toremove an anatomical portion or feature of the eye, including but notlimited to the trabecular meshwork, the iris, the cornea, or aqueoushumor. The methods of the invention are also preferably conductedwithout inducing substantial ocular inflammation, such assubconjunctival blebbing or endophthalmitis. Such methods can beachieved using an ab interno approach by inserting the hollow shaftconfigured to hold the intraocular shunt through the cornea, across theanterior chamber, through the trabecular meshwork and sclera and intothe intra-Tenon's space. However, the methods of the invention may beconducted using an ab externo approach.

In another embodiment, the methods of the invention further involvesinjecting an aqueous solution into the eye below Tenon's capsule inorder to to balloon the capsule away from the sclera. The increase inintra-Tenon's space caused by the ballooning of Tenon's capsule ishelpful for positioning of the outlet of the shunt in the intra-Tenon'sspace. The solution is injected prior to the shaft piercing the scleraand entering the intra-Tenon's space. Suitable aqueous solutions includebut are not limited to Dulbecco's Phosphate Buffered Saline (DPBS),Hank's Balanced Salt Solution (HBSS), Phosphate-Buffered Saline (PBS),Earle's Balanced Salt Solution (EBSS), or other balanced salt solutionsknown in the art. In some embodiments, the methods of the inventioninvolve injecting a viscoelastic fluid into the eye. Preferably, themethods of the invention are conducted without the use of a viscoelasticfluid.

When the methods of the invention are conducted using an ab internoapproach, the angle of entry through the cornea affects optimalplacement of the shunt in the intra-Tenon's space. Preferably, thehollow shaft is inserted into the eye at an angle above or below thecorneal limbus, in contrast with entering through the corneal limbus.For example, the hollow shaft is inserted approximately 0.25 to 3.0 mm,preferably approximately 0.5 to 2.5 mm, more preferably approximately1.0 mm to 2.0 mm above the corneal limbus, or any specific value withinsaid ranges, e.g., approximately 1.0 mm, approximately 1.1 mm,approximately 1.2 mm, approximately 1.3 mm, approximately 1.4 mm,approximately 1.5 mm, approximately 1.6 mm, approximately 1.7 mm,approximately 1.8 mm, approximately 1.9 mm or approximately 2.0 mm abovethe corneal limbus.

Without intending to be bound by any theory, placement of the shuntfarther from the limbus at the exit site, as provided by an angle ofentry above the limbus, is believed to provide access to more lymphaticchannels for drainage of aqueous humor, such as the episcleral lymphaticnetwork, in addition to the conjunctival lymphatic system. A higherangle of entry also results in flatter placement in the intra-Tenon'sspace so that there is less bending of the shunt, less pressure onTenon's capsule, and subsequently less erosion pressure on theconjunctiva via Tenon's capsule.

For example, as shown in FIG. 6A, shaft entry at the limbus 52 resultsin exit site distance 53 of approximately 1.6 mm from the limbus, andvery close proximity to the iris 4. Such placement results in a largedegree of bending of the shunt, resulting in increased pressure onTenon's capsule and subsequently on the conjunctiva. In contrast, a highangle of entry 54 above the limbus 52 (e.g., 2 mm above the limbus 52),results in an exit site distance 53 of approximately 2.1 mm from thelimbus and a height well above the iris 4, as shown in FIG. 6B. Suchplacement results in flatter placement in the intra-Tenon's space sothat there is less bending of the shunt, less pressure on Tenon'scapsule, and subsequently less erosion pressure on the conjunctiva viaTenon's capsule.

In certain embodiments, to ensure proper positioning and functioning ofthe intraocular shunt, the depth of penetration through the sclera isimportant when conducting the methods of the invention, In oneembodiment, the distal tip of the hollow shaft pierces the sclerawithout coring, removing or causing major tissue distortion of thesurrounding eye tissue. The shunt is then deployed from the shaft.Preferably, a distal portion of the hollow shaft (as opposed to thedistal tip) completely penetrates the sclera before the shunt isdeployed from the hollow shaft. In certain embodiments, the hollow shaftis a flat bevel needle, such as a needle having a triple-ground point.The tip bevel first pierces through the sclera making a horizontal slit.In a preferred embodiment of the methods of the invention, the needle isadvanced even further such that the entire flat bevel penetrates throughthe sclera, as shown in FIG. 7D, to spread and open the tissue to a fullcircular diameter. The tip bevel and flat bevel portions of a tripleground needle point, and the configuration of the shunt disposed in theneedle point, are exemplified as the gray shaded areas in FIGS. 7A-7C.Without intending to be bound by any theory, if the scleral channel isnot completely forced open by the flat bevel portion of the needle, thematerial around the opening may not be sufficiently stretched and apinching of the implant in that zone will likely occur, causing theshunt to fail. Full penetration of the flat bevel through the scleracauses minor distortion and trauma to the local area. However, this areaultimately surrounds and conforms to the shunt once the shunt isdeployed in the eye.

FIG. 8A depicts an example of an intraocular shunt implanted in an eyein accordance with the methods of the invention using a triple groundneed point with 100% penetration of the flat bevel in the scleralchannel. FIG. 8B depicts an example of a shunt implanted in an eye inaccordance with the methods of the invention using a triple groundneedle point with approximately 50% penetration of the flat bevel in thescleral channel. As shown in FIG. 8B, the shunt is almost completelypinched off as compared to the open shunt depicted in FIG. 8A.

The methods of the invention may be conducted using any commerciallyavailable shunts, such as the Optonol Ex-PRESS™ mini Glaucoma shunt, andthe Solx DeepLight Gold™ Micro-Shunt. However, the methods of theinvention are preferably conducted using the intraocular shunts of thepresent invention, as described herein.

Intraocular Shunts of the Invention

The present invention provides intraocular shunts that are configured toform a drainage pathway from the anterior chamber of the eye to theintra-Tenon's space. In particular, the intraocular shunts of theinvention have a length that is sufficient to form a drainage pathwayfrom the anterior chamber of the eye to the intra-Tenon's space. Thelength of the shunt is important for achieving placement specifically inthe intra-Tenon's space. A shunt that is too long will extend beyond theintra-Tenon's space and irritate the conjunctiva which can cause thefiltration procedure to fail, as previously described. A shunt that istoo short will not provide sufficient access to drainage pathways suchas the episcleral lymphatic system or the conjunctival lymphatic system.

Shunts of the invention may be any length that allows for drainage ofaqueous humor from an anterior chamber of an eye to the intra-tenon'sspace. Exemplary shunts range in length from approximately 0.5 mm toapproximately 20 mm or between approximately 4 mm to approximately 16mm, or any specific value within said ranges. In certain embodiments,the length of the shunt is between approximately 6 to 8 mm, or anyspecific value within said range, e.g., 6.0 mm, 6.1 mm, 6.2 mm, 6.3 mm,6.4 mm, 6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9 mm, 7 mm, 7.1 mm, 7.2 mm,7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm. 7.9 mm, or 8.0 mm.

The intraocular shunts of the invention are particularly suitable foruse in an ab interno glaucoma filtration procedure. Commerciallyavailable shunts that are currently used in ab interno filtrationprocedures are typically made of a hard, inflexible material such asgold, polymer, titanium, or stainless steel, and cause substantialirritation of the eye tissue, resulting in ocular inflammation such assubconjunctival blebbing or endophthalmitis. In contrast, theintraocular shunts of the invention are flexible, and have an elasticitymodulus that is substantially identical to the elasticity modulus of thesurrounding tissue in the implant site. As such, the intraocular shuntsof the invention are easily bendable, do not erode or cause a tissuereaction, and do not migrate once implanted. Thus, when implanted in theeye using an ab interno procedure, such as the methods described herein,the intraocular shunts of the invention do not induce substantial ocularinflammation such as subconjunctival blebbing or endophthalmitis.Additional exemplary features of the intraocular shunts of the inventionare discussed in further detail below.

Tissue Compatible Shunts

In certain aspects, the invention generally provides shunts composed ofa material that has an elasticity modulus that is compatible with anelasticity modulus of tissue surrounding the shunt. In this manner,shunts of the invention are flexibility matched with the surroundingtissue, and thus will remain in place after implantation without theneed for any type of anchor that interacts with the surrounding tissue.Consequently, shunts of the invention will maintain fluid flow away foran anterior chamber of the eye after implantation without causingirritation or inflammation to the tissue surrounding the eye.

Elastic modulus, or modulus of elasticity, is a mathematical descriptionof an object or substance's tendency to be deformed elastically when aforce is applied to it. The elastic modulus of an object is defined asthe slope of its stress-strain curve in the elastic deformation region:

$\lambda \overset{def}{=}\frac{stress}{strain}$

where lambda (λ) is the elastic modulus; stress is the force causing thedeformation divided by the area to which the force is applied; andstrain is the ratio of the change caused by the stress to the originalstate of the object. The elasticity modulus may also be known as Young'smodulus (E), which describes tensile elasticity, or the tendency of anobject to deform along an axis when opposing forces are applied alongthat axis. Young's modulus is defined as the ratio of tensile stress totensile strain. For further description regarding elasticity modulus andYoung's modulus, see for example Gere (Mechanics of Materials, 6^(th)Edition, 2004, Thomson), the content of which is incorporated byreference herein in its entirety.

The elasticity modulus of any tissue can be determined by one of skillin the art. See for example Samani et al. (Phys. Med. Biol. 48:2183,2003); Erkamp et al. (Measuring The Elastic Modulus Of Small TissueSamples, Biomedical Engineering Department and Electrical Engineeringand Computer Science Department University of Michigan Ann Arbor, Mich.48109-2125; and Institute of Mathematical Problems in Biology RussianAcademy of Sciences, Pushchino, Moscow Region 142292 Russia); Chen etal. (IEEE Trans. Ultrason. Ferroelec. Freq. Control 43:191-194, 1996);Hall, (In 1996 Ultrasonics Symposium Proc., pp. 1193-1196, IEEE Cat. No.96CH35993, IEEE, New York, 1996); and Parker (Ultrasound Med. Biol.16:241-246, 1990), each of which provides methods of determining theelasticity modulus of body tissues. The content of each of these isincorporated by reference herein in its entirety.

The elasticity modulus of tissues of different organs is known in theart. For example, Pierscionek et al. (Br J Ophthalmol, 91:801-803, 2007)and Friberg (Experimental Eye Research, 473:429-436, 1988) show theelasticity modulus of the cornea and the sclera of the eye. The contentof each of these references is incorporated by reference herein in itsentirety. Chen, Hall, and Parker show the elasticity modulus ofdifferent muscles and the liver. Erkamp shows the elasticity modulus ofthe kidney.

Shunts of the invention are composed of a material that is compatiblewith an elasticity modulus of tissue surrounding the shunt. In certainembodiments, the material has an elasticity modulus that issubstantially identical to the elasticity modulus of the tissuesurrounding the shunt. In other embodiments, the material has anelasticity modulus that is greater than the elasticity modulus of thetissue surrounding the shunt. Exemplary materials includes biocompatiblepolymers, such as polycarbonate, polyethylene, polyethyleneterephthalate, polyimide, polystyrene, polypropylene,poly(styrene-b-isobutylene-b-styrene), or silicone rubber.

In particular embodiments, shunts of the invention are composed of amaterial that has an elasticity modulus that is compatible with theelasticity modulus of tissue in the eye, particularly scleral tissue. Incertain embodiments, compatible materials are those materials that aresofter than scleral tissue or marginally harder than scleral tissue, yetsoft enough to prohibit shunt migration. The elasticity modulus foranterior scleral tissue is approximately 2.9±1.4×10⁶ N/m², and1.8±1.1×10⁶ N/m² for posterior scleral tissue. See Friberg (ExperimentalEye Research, 473:429-436, 1988). An exemplary material is cross linkedgelatin derived from Bovine or Porcine Collagen.

The invention encompasses shunts of different shapes and differentdimensions, and the shunts of the invention may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 190 μm to approximately 300 μm, and a lengthfrom approximately 0.5 mm to approximately 20 mm.

Shunts Reactive to Pressure

In other aspects, the invention generally provides shunts in which aportion of the shunt is composed of a flexible material that is reactiveto pressure, i.e., the diameter of the flexible portion of the shuntfluctuates depending upon the pressures exerted on that portion of theshunt. FIG. 9 provides a schematic of a shunt 23 having a flexibleportion 51 (thicker black lines). In this figure, the flexible portion51 is shown in the middle of the shunt 23. However, the flexible portion51 may be located in any portion of the shunt, such as the proximal ordistal portion of the shunt. In certain embodiments, the entire shunt iscomposed of the flexible material, and thus the entire shunt is flexibleand reactive to pressure.

The flexible portion 51 of the shunt 23 acts as a valve that regulatesfluid flow through the shunt. The human eye produces aqueous humor at arate of about 2 μl/min for approximately 3 ml/day. The entire aqueousvolume is about 0.25 ml. When the pressure in the anterior chamber fallsafter surgery to about 7-8 mmHg, it is assumed the majority of theaqueous humor is exiting the eye through the implant since venousbackpressure prevents any significant outflow through normal drainagestructures (e.g., the trabecular meshwork).

After implantation, intraocular shunts have pressure exerted upon themby tissues surrounding the shunt (e.g., scleral tissue such as thesclera channel and the sclera exit) and pressure exerted upon them byaqueous humor flowing through the shunt. The flow through the shunt, andthus the pressure exerted by the fluid on the shunt, is calculated bythe equation:

$\Phi = {\frac{V}{t} = {{v\; \pi \; R^{2}} = {{\frac{\pi \; R^{4}}{8\eta}\left( \frac{{- \Delta}\; P}{\Delta \; x} \right)} = {\frac{\pi \; R^{4}}{8\eta}\frac{{\Delta \; P}}{L}}}}}$

where Φ is the volumetric flow rate; V is a volume of the liquid poured(cubic meters); t is the time (seconds); ν is mean fluid velocity alongthe length of the tube (meters/second); χ is a distance in direction offlow (meters); R is the internal radius of the tube (meters); ΔP is thepressure difference between the two ends (pascals); η is the dynamicfluid viscosity (pascal-second (Pa·s)); and L is the total length of thetube in the x direction (meters).

FIG. 10A provides a schematic of a shunt 26 implanted into an eye forregulation of fluid flow from the anterior chamber of the eye to an areaof lower pressure (e.g., the intra-Tenon's space, the subconjunctivalspace, the episcleral vein, the suprachoroidal space, or Schlemm'scanal). In certain embodiments, the area of lower pressure is thesubarachnoid space. The shunt is implanted such that a proximal end 27of the shunt 26 resides in the anterior chamber 28 of the eye, and adistal end 29 of the shunt 26 resides outside of the anterior chamber toconduct aqueous humor from the anterior chamber to an area of lowerpressure. A flexible portion 30 (thicker black lines) of the shunt 26spans at least a portion of the sclera of the eye. As shown in FIG. 10A,the flexible portion spans an entire length of the sclera 21.

When the pressure exerted on the flexible portion 30 of the shunt 26 bysclera 31 (vertical arrows) is greater than the pressure exerted on theflexible portion 30 of the shunt 26 by the fluid flowing through theshunt (horizontal arrow), the flexible portion 30 decreases in diameter,restricting flow through the shunt 26 (FIG. 10B). The restricted flowresults in aqueous humor leaving the anterior chamber 28 at a reducedrate.

When the pressure exerted on the flexible portion 20 of the shunt 26 bythe fluid flowing through the shunt (horizontal arrow) is greater thanthe pressure exerted on the flexible portion 30 of the shunt 26 by thesclera 31 (vertical arrows), the flexible portion 30 increases indiameter, increasing flow through the shunt 26 (FIG. 10C). The increasedflow results in aqueous humor leaving the anterior chamber 28 at anincreased rate.

The invention encompasses shunts of different shapes and differentdimensions, and the shunts of the invention may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 190 μm to approximately 300 μm, and a lengthfrom approximately 0.5 mm to approximately 20 mm.

In a particular embodiments, the shunt has a length of about 6 mm and aninner diameter of about 64 μm. With these dimensions, the pressuredifference between the proximal end of the shunt that resides in theanterior chamber and the distal end of the shunt that resides outsidethe anterior chamber is about 4.3 mmHg. Such dimensions thus allow theimplant to act as a controlled valve and protect the integrity of theanterior chamber.

It will be appreciated that different dimensioned implants may be used.For example, shunts that range in length from about 0.5 mm to about 20mm and have a range in inner diameter from about 10 μm to about 100 μmallow for pressure control from approximately 0.5 mmHg to approximately20 mmHg.

The material of the flexible portion and the thickness of the wall ofthe flexible portion will determine how reactive the flexible portion isto the pressures exerted upon it by the surrounding tissue and the fluidflowing through the shunt. Generally, with a certain material, thethicker the flexible portion, the less responsive the portion will be topressure. In certain embodiments, the flexible portion is a gelatin orother similar material, and the thickness of the gelatin materialforming the wall of the flexible portion ranges from about 10 μm thickto about 100 μm thick.

In a certain embodiment, the gelatin used for making the flexibleportion is known as gelatin Type B from bovine skin. An exemplarygelatin is PB Leiner gelatin from bovine skin, Type B, 225 Bloom, USP.Another material that may be used in the making of the flexible portionis a gelatin Type A from porcine skin, also available from SigmaChemical. Such gelatin is available from Sigma Chemical Company of St.Louis, Mo. under Code G-9382. Still other suitable gelatins includebovine bone gelatin, porcine bone gelatin and human-derived gelatins. Inaddition to gelatins, the flexible portion may be made of hydroxypropylmethycellulose (HPMC), collagen, polylactic acid, polylglycolic acid,hyaluronic acid and glycosaminoglycans.

In certain embodiments, the gelatin is cross-linked. Cross-linkingincreases the inter- and intramolecular binding of the gelatinsubstrate. Any method for cross-linking the gelatin may be used. In aparticular embodiment, the formed gelatin is treated with a solution ofa cross-linking agent such as, but not limited to, glutaraldehyde. Othersuitable compounds for cross-linking include1-ethyl-3-[3-(dimethyamino)propyl]carbodiimide (EDC). Cross-linking byradiation, such as gamma or electron beam (e-beam) may be alternativelyemployed.

In one embodiment, the gelatin is contacted with a solution ofapproximately 25% glutaraldehyde for a selected period of time. Onesuitable form of glutaraldehyde is a grade 1G5882 glutaraldehydeavailable from Sigma Aldridge Company of Germany, although otherglutaraldehyde solutions may also be used. The pH of the glutaraldehydesolution should be in the range of 7 to 7.8 and, more particularly,7.35-7.44 and typically approximately 7.4+/−0.01. If necessary, the pHmay be adjusted by adding a suitable amount of a base such as sodiumhydroxide as needed.

Methods for forming the flexible portion of the shunt are shown forexample in Yu et al. (U.S. patent application number 2008/0108933), thecontent of which is incorporated by reference herein in its entirety. Inan exemplary protocol, the flexible portion may be made by dipping acore or substrate such as a wire of a suitable diameter in a solution ofgelatin. The gelatin solution is typically prepared by dissolving agelatin powder in de-ionized water or sterile water for injection andplacing the dissolved gelatin in a water bath at a temperature ofapproximately 55° C. with thorough mixing to ensure complete dissolutionof the gelatin. In one embodiment, the ratio of solid gelatin to wateris approximately 10% to 50% gelatin by weight to 50% to 90% by weight ofwater. In an embodiment, the gelatin solution includes approximately 40%by weight, gelatin dissolved in water. The resulting gelatin solutionshould be devoid of air bubbles and has a viscosity that is betweenapproximately 200-500 cp and more particularly between approximately 260and 410 cp (centipoise).

Once the gelatin solution has been prepared, in accordance with themethod described above, supporting structures such as wires having aselected diameter are dipped into the solution to form the flexibleportion. Stainless steel wires coated with a biocompatible, lubriciousmaterial such as polytetrafluoroethylene (Teflon) are preferred.

Typically, the wires are gently lowered into a container of the gelatinsolution and then slowly withdrawn. The rate of movement is selected tocontrol the thickness of the coat. In addition, it is preferred that athe tube be removed at a constant rate in order to provide the desiredcoating. To ensure that the gelatin is spread evenly over the surface ofthe wire, in one embodiment, the wires may be rotated in a stream ofcool air which helps to set the gelatin solution and affix film onto thewire. Dipping and withdrawing the wire supports may be repeated severaltimes to further ensure even coating of the gelatin. Once the wires havebeen sufficiently coated with gelatin, the resulting gelatin films onthe wire may be dried at room temperature for at least 1 hour, and morepreferably, approximately 10 to 24 hours. Apparatus for forming gelatintubes are described in Yu et al. (U.S. patent application number2008/0108933).

Once dried, the formed flexible portions may be treated with across-linking agent. In one embodiment, the formed flexible portion maybe cross-linked by dipping the wire (with film thereon) into the 25%glutaraldehyde solution, at pH of approximately 7.0-7.8 and morepreferably approximately 7.35-7.44 at room temperature for at least 4hours and preferably between approximately 10 to 36 hours, depending onthe degree of cross-linking desired. In one embodiment, the formedflexible portion is contacted with a cross-linking agent such asgluteraldehyde for at least approximately 16 hours. Cross-linking canalso be accelerated when it is performed a high temperatures. It isbelieved that the degree of cross-linking is proportional to thebioabsorption time of the shunt once implanted. In general, the morecross-linking, the longer the survival of the shunt in the body.

The residual glutaraldehyde or other cross-linking agent is removed fromthe formed flexible portion by soaking the tubes in a volume of sterilewater for injection. The water may optionally be replaced at regularintervals, circulated or re-circulated to accelerate diffusion of theunbound glutaraldehyde from the tube. The tubes are washed for a periodof a few hours to a period of a few months with the ideal time being3-14 days. The now cross-linked gelatin tubes may then be dried (cured)at ambient temperature for a selected period of time. It has beenobserved that a drying period of approximately 48-96 hours and moretypically 3 days (i.e., 72 hours) may be preferred for the formation ofthe cross-linked gelatin tubes.

Where a cross-linking agent is used, it may be desirable to include aquenching agent in the method of making the flexible portion. Quenchingagents remove unbound molecules of the cross-linking agent from theformed flexible portion. In certain cases, removing the cross-linkingagent may reduce the potential toxicity to a patient if too much of thecross-linking agent is released from the flexible portion. In certainembodiments, the formed flexible portion is contacted with the quenchingagent after the cross-linking treatment and, may be included with thewashing/rinsing solution. Examples of quenching agents include glycineor sodium borohydride.

After the requisite drying period, the formed and cross-linked flexibleportion is removed from the underlying supports or wires. In oneembodiment, wire tubes may be cut at two ends and the formed gelatinflexible portion slowly removed from the wire support. In anotherembodiment, wires with gelatin film thereon, may be pushed off using aplunger or tube to remove the formed gelatin flexible portion.

Multi-Port Shunts

Other aspects of the invention generally provide multi-port shunts. Suchshunts reduce probability of the shunt clogging after implantationbecause fluid can enter or exit the shunt even if one or more ports ofthe shunt become clogged with particulate. In certain embodiments, theshunt includes a hollow body defining a flow path and more than twoports, in which the body is configured such that a proximal portionreceives fluid from the anterior chamber of an eye and a distal portiondirects the fluid to the intra-Tenon's space.

The shunt may have many different configurations. FIG. 11A shows anembodiment of a shunt 32 in which the proximal portion of the shunt(i.e., the portion disposed within the anterior chamber of the eye)includes more than one port (designated as numbers 33 a to 33 e) and thedistal portion of the shunt (i.e., the portion that is located in theintra-Tenon's space) includes a single port 34. FIG. 11B shows anotherembodiment of a shunt 32 in which the proximal portion includes a singleport 33 and the distal portion includes more than one port (designatedas numbers 34 a to 34 e). FIG. 11C shows another embodiment of a shunt32 in which the proximal portions include more than one port (designatedas numbers 33 a to 33 e) and the distal portions include more than oneport (designated as numbers 34 a to 34 e). While FIG. 11 shows shuntshave five ports at the proximal portion, distal portion, or both, thoseshunts are only exemplary embodiments. The ports may be located alongany portion of the shunt, and shunts of the invention include all shuntshaving more than two ports. For example, shunts of the invention mayinclude at least three ports, at least four ports, at least five ports,at least 10 ports, at least 15 ports, or at least 20 ports.

The ports may be positioned in various different orientations and alongvarious different portions of the shunt. In certain embodiments, atleast one of the ports is oriented at an angle to the length of thebody. In certain embodiments, at least one of the ports is oriented 90°to the length of the body. See for example FIG. 11A, which depicts ports33 a, 33 b, 33 d, and 33 e as being oriented at a 90° angle to port 33c.

The ports may have the same or different inner diameters. In certainembodiments, at least one of the ports has an inner diameter that isdifferent from the inner diameters of the other ports. FIG. 12 shows anembodiment of a shunt 32 having multiple ports (33 a and 33 b) at aproximal end and a single port 34 at a distal end. FIG. 12A shows thatport 33 b has an inner diameter that is different from the innerdiameters of ports 33 a and 34. In this figure, the inner diameter ofport 33 b is less than the inner diameter of ports 33 a and 34. Anexemplary inner diameter of port 33 b is from about 20 μm to about 40μm, particularly about 30 μm. In other embodiments, the inner diameterof port 33 b is greater than the inner diameter of ports 33 a and 34.See for example FIG. 12B.

The invention encompasses shunts of different shapes and differentdimensions, and the shunts of the invention may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 190 μm to approximately 300 μm, and a lengthfrom approximately 0.5 mm to approximately 20 mm. Shunts of theinvention may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts with Overflow Ports

Other aspects of the invention generally provide shunts with overflowports. Those shunts are configured such that the overflow port remainspartially or completely closed until there is a pressure build-up withinthe shunt sufficient to force open the overflow port. Such pressurebuild-up typically results from particulate partially or fully cloggingan entry or an exit port of the shunt. Such shunts reduce probability ofthe shunt clogging after implantation because fluid can enter or exitthe shunt by the overflow port even in one port of the shunt becomesclogged with particulate.

In certain embodiments, the shunt includes a hollow body defining aninlet configured to receive fluid from an anterior chamber of an eye andan outlet configured to direct the fluid to the intra-Tenon's space, thebody further including at least one slit. The slit may be located at anyplace along the body of the shunt. FIG. 13A shows a shunt 35 having aninlet 36, an outlet 37, and a slit 38 located in proximity to the inlet36. FIG. 13B shows a shunt 35 having an inlet 36, an outlet 37, and aslit 39 located in proximity to the outlet 37. FIG. 13C shows a shunt 35having an inlet 36, an outlet 37, a slit 38 located in proximity to theinlet 36, and a slit 39 located in proximity to the outlet 37.

While FIG. 13 shows shunts have only a single overflow port at theproximal portion, the distal portion, or both the proximal and distalportions, those shunts are only exemplary embodiments. The overflowport(s) may be located along any portion of the shunt, and shunts of theinvention include shunts having more than one overflow port. In certainembodiments, shunts of the invention include more than one overflow portat the proximal portion, the distal portion, or both. For example, FIG.14 shows a shunt 40 having an inlet 41, an outlet 42, and slits 43 a and43 b located in proximity to the inlet 41. Shunts of the invention mayinclude at least two overflow ports, at least three overflow ports, atleast four overflow ports, at least five overflow ports, at least 10overflow ports, at least 15 overflow ports, or at least 20 overflowports. In certain embodiments, shunts of the invention include two slitsthat overlap and are oriented at 90° to each other, thereby forming across.

In certain embodiments, the slit may be at the proximal or the distalend of the shunt, producing a split in the proximal or the distal end ofthe implant. FIG. 15 shows an embodiment of a shunt 44 having an inlet45, outlet 46, and a slit 47 that is located at the proximal end of theshunt, producing a split in the inlet 45 of the shunt.

In certain embodiments, the slit has a width that is substantially thesame or less than an inner diameter of the inlet. In other embodiments,the slit has a width that is substantially the same or less than aninner diameter of the outlet. In certain embodiments, the slit has alength that ranges from about 0.05 mm to about 2 mm, and a width thatranges from about 10 μm to about 200 μm. Generally, the slit does notdirect the fluid unless the outlet is obstructed. However, the shunt maybe configured such that the slit does direct at least some of the fluideven if the inlet or outlet is not obstructed.

The invention encompasses shunts of different shapes and differentdimensions, and the shunts of the invention may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 190 μm to approximately 300 μm, and a lengthfrom approximately 0.5 mm to approximately 20 mm. Shunts of theinvention may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts Having a Variable Inner Diameter

In other aspects, the invention generally provides a shunt having avariable inner diameter. In particular embodiments, the diameterincreases from inlet to outlet of the shunt. By having a variable innerdiameter that increases from inlet to outlet, a pressure gradient isproduced and particulate that may otherwise clog the inlet of the shuntis forced through the inlet due to the pressure gradient. Further, theparticulate will flow out of the shunt because the diameter onlyincreases after the inlet.

FIG. 16 shows an embodiment of a shunt 48 having an inlet 49 configuredto receive fluid from an anterior chamber of an eye and an outlet 50configured to direct the fluid to a location of lower pressure withrespect to the anterior chamber, in which the body further includes avariable inner diameter that increases along the length of the body fromthe inlet 49 to the outlet 50. In certain embodiments, the innerdiameter continuously increases along the length of the body, forexample as shown in FIG. 16. In other embodiments, the inner diameterremains constant along portions of the length of the body.

In exemplary embodiments, the inner diameter may range in size fromabout 10 μm to about 200 μm, and the inner diameter at the outlet mayrange in size from about 15 μm to about 300 μm. The inventionencompasses shunts of different shapes and different dimensions, and theshunts of the invention may be any shape or any dimension that may beaccommodated by the eye. In certain embodiments, the intraocular shuntis of a cylindrical shape and has an outside cylindrical wall and ahollow interior. The shunt may have an inside diameter fromapproximately 10 μm to approximately 250 μm, an outside diameter fromapproximately 190 μm to approximately 300 μm, and a length fromapproximately 0.5 mm to approximately 20 mm. Shunts of the invention maybe made from any biocompatible material. An exemplary material isgelatin. Methods of making shunts composed of gelatin are describedabove.

Pharmaceutical Agents

In certain embodiments, shunts of the invention may be coated orimpregnated with at least one pharmaceutical and/or biological agent ora combination thereof. The pharmaceutical and/or biological agent maycoat or impregnate an entire exterior of the shunt, an entire interiorof the shunt, or both. Alternatively, the pharmaceutical or biologicalagent may coat and/or impregnate a portion of an exterior of the shunt,a portion of an interior of the shunt, or both. Methods of coatingand/or impregnating an intraocular shunt with a pharmaceutical and/orbiological agent are known in the art. See for example, Darouiche (U.S.Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487; 5,902,283;5,853,745; and 5,624,704) and Yu et al. (U.S. patent application serialnumber 2008/0108933). The content of each of these references isincorporated by reference herein its entirety.

In certain embodiments, the exterior portion of the shunt that residesin the anterior chamber after implantation (e.g., about 1 mm of theproximal end of the shunt) is coated and/or impregnated with thepharmaceutical or biological agent. In other embodiments, the exteriorof the shunt that resides in the scleral tissue after implantation ofthe shunt is coated and/or impregnated with the pharmaceutical orbiological agent. In other embodiments, the exterior portion of theshunt that resides in the intra-Tenon's space after implantation iscoated and/or impregnated with the pharmaceutical or biological agent.In embodiments in which the pharmaceutical or biological agent coatsand/or impregnates the interior of the shunt, the agent may be flushedthrough the shunt and into the area of lower pressure (e.g., theintra-Tenon's space or the subconjunctival space).

Any pharmaceutical and/or biological agent or combination thereof may beused with shunts of the invention. The pharmaceutical and/or biologicalagent may be released over a short period of time (e.g., seconds) or maybe released over longer periods of time (e.g., days, weeks, months, oreven years). Exemplary agents include anti-mitotic pharmaceuticals suchas Mitomycin-C or 5-Fluorouracil, anti-VEGF (such as Lucintes, Macugen,Avastin, VEGF or steroids).

Deployment Devices

Deployment into the eye of an intraocular shunt according to theinvention can be achieved using a hollow shaft configured to hold theshunt, as described herein. The hollow shaft can be coupled to adeployment device or part of the deployment device itself. Deploymentdevices that are suitable for deploying shunts according to theinvention include but are not limited to the deployment devicesdescribed in U.S. Pat. No. 6,007,511, U.S. Pat. No. 6,544,249, and U.S.Publication No. US2008/0108933, the contents of which are eachincorporated herein by reference in their entireties. In otherembodiments, the deployment devices are devices as described inco-pending and co-owned U.S. nonprovisional patent application Ser. No.12/946,222 filed on Nov. 15, 2010, and having Attorney Docket No.AQUE-002/01US 29053/15, the entire content of which is incorporated byreference herein.

In still other embodiments, the shunts according to the invention aredeployed into the eye using the deployment device 100 depicted in FIG.17. While FIG. 17 shows a handheld manually operated shunt deploymentdevice, it will be appreciated that devices of the invention may becoupled with robotic systems and may be completely or partiallyautomated. As shown in FIG. 17, deployment device 100 includes agenerally cylindrical body or housing 101, however, the body shape ofhousing 101 could be other than cylindrical. Housing 101 may have anergonomical shape, allowing for comfortable grasping by an operator.Housing 101 is shown with optional grooves 102 to allow for easiergripping by a surgeon.

Housing 101 is shown having a larger proximal portion that tapers to adistal portion. The distal portion includes a hollow sleeve 105. Thehollow sleeve 105 is configured for insertion into an eye and to extendinto an anterior chamber of an eye. The hollow sleeve is visible withinan anterior chamber of an eye. The sleeve may include an edge at adistal end that provides resistance feedback to an operator uponinsertion of the deployment device 100 within an eye of a person. Uponadvancement of the device 100 across an anterior chamber of the eye, thehollow sleeve 105 will eventually contact the sclera, providingresistance feedback to an operator that no further advancement of thedevice 100 is necessary. The edge of the sleeve 105, prevents the shaft104 from accidentally being pushed too far through the sclera. Atemporary guard 108 is configured to fit around sleeve 105 and extendbeyond an end of sleeve 105. The guard is used during shipping of thedevice and protects an operator from a distal end of a hollow shaft 104that extends beyond the end of the sleeve 105. The guard is removedprior to use of the device.

Housing 101 is open at its proximal end, such that a portion of adeployment mechanism 103 may extend from the proximal end of the housing101. A distal end of housing 101 is also open such that at least aportion of a hollow shaft 104 may extend through and beyond the distalend of the housing 101. Housing 101 further includes a slot 106 throughwhich an operator, such as a surgeon, using the device 100 may view anindicator 107 on the deployment mechanism 103.

Housing 101 may be made of any material that is suitable for use inmedical devices. For example, housing 101 may be made of a lightweightaluminum or a biocompatible plastic material. Examples of such suitableplastic materials include polycarbonate and other polymeric resins suchas DELRIN and ULTEM. In certain embodiments, housing 101 is made of amaterial that may be autoclaved, and thus allow for housing 101 to bere-usable. Alternatively, device 100, may be sold as a one-time-usedevice, and thus the material of the housing does not need to be amaterial that is autoclavable.

Housing 101 may be made of multiple components that connect together toform the housing. FIG. 18 shows an exploded view of deployment device100. In this figure, housing 101, is shown having three components 101a, 101 b, and 101 c. The components are designed to screw together toform housing 101. FIG. 18 also shows deployment mechanism 103. Thehousing 101 is designed such that deployment mechanism 103 fits withinassembled housing 101. Housing 101 is designed such that components ofdeployment mechanism 103 are movable within housing 101.

FIGS. 19A to 19D show different enlarged views of the deploymentmechanism 103. Deployment mechanism 103 may be made of any material thatis suitable for use in medical devices. For example, deploymentmechanism 103 may be made of a lightweight aluminum or a biocompatibleplastic material. Examples of such suitable plastic materials includepolycarbonate and other polymeric resins such as DELRIN and ULTEM. Incertain embodiments, deployment mechanism 103 is made of a material thatmay be autoclaved, and thus allow for deployment mechanism 103 to bere-usable. Alternatively, device 100 may be sold as a one-time-usedevice, and thus the material of the deployment mechanism does not needto be a material that is autoclavable.

Deployment mechanism 103 includes a proximal portion 109 and a distalportion 110. The deployment mechanism 103 is configured such thatproximal portion 109 is movable within distal portion 110. Moreparticularly, proximal portion 109 is capable of partially retracting towithin distal portion 110.

In this embodiment, the proximal portion 109 is shown to taper to aconnection with a hollow shaft 104. This embodiment is illustrated suchthat the connection between the hollow shaft 104 and the proximalportion 109 of the deployment mechanism 103 occurs inside the housing101. In other embodiments, the connection between hollow shaft 104 andthe proximal portion 109 of the deployment mechanism 103 may occuroutside of the housing 101. Hollow shaft 104 may be removable from theproximal portion 109 of the deployment mechanism 103. Alternatively, thehollow shaft 104 may be permanently coupled to the proximal portion 109of the deployment mechanism 103.

Generally, hollow shaft 104 is configured to hold an intraocular shunt,such as the intraocular shunts according to the invention. The shaft 104may be any length. A usable length of the shaft may be anywhere fromabout 5 mm to about 40 mm, and is 15 mm in certain embodiments. Incertain embodiments, the shaft is straight. In other embodiments, shaftis of a shape other than straight, for example a shaft having a bendalong its length or a shaft as depicted in FIGS. 5A-5C.

A distal portion of the deployment mechanism includes optional grooves116 to allow for easier gripping by an operator for easier rotation ofthe deployment mechanism, which will be discussed in more detail below.The distal portion 110 of the deployment mechanism also includes atleast one indicator that provides feedback to an operator as to thestate of the deployment mechanism. The indicator may be any type ofindicator know in the art, for example a visual indicator, an audioindicator, or a tactile indicator. FIG. 19 shows a deployment mechanismhaving two indicators, a ready indicator 111 and a deployed indicator119. Ready indicator 111 provides feedback to an operator that thedeployment mechanism is in a configuration for deployment of anintraocular shunt from the deployment device 100. The indicator 111 isshown in this embodiment as a green oval having a triangle within theoval. Deployed indicator 119 provides feedback to the operator that thedeployment mechanism has been fully engaged and has deployed the shuntfrom the deployment device 100. The deployed indicator 119 is shown inthis embodiment as a yellow oval having a black square within the oval.The indicators are located on the deployment mechanism such that whenassembled, the indicators 111 and 119 may be seen through slot 106 inhousing 101.

The distal portion 110 includes a stationary portion 110 b and arotating portion 110 a. The distal portion 110 includes a channel 112that runs part of the length of stationary portion 110 b and the entirelength of rotating portion 110 a. The channel 112 is configured tointeract with a protrusion 117 on an interior portion of housingcomponent 101 a (FIGS. 20A and 20B). During assembly, the protrusion 117on housing component 101 a is aligned with channel 112 on the stationaryportion 110 b and rotating portion 110 a of the deployment mechanism103. The distal portion 110 of deployment mechanism 103 is slid withinhousing component 101 a until the protrusion 117 sits within stationaryportion 110 b (FIG. 20C). Assembled, the protrusion 117 interacts withthe stationary portion 110 b of the deployment mechanism 103 andprevents rotation of stationary portion 110 b. In this configuration,rotating portion 110 a is free to rotate within housing component 101 a.

Referring back to FIG. 19, the rotating portion 110 a of distal portion110 of deployment mechanism 103 also includes channels 113 a, 113 b, and113 c. Channel 113 a includes a first portion 113 a 1 that is straightand runs perpendicular to the length of the rotating portion 110 a, anda second portion 113 a 2 that runs diagonally along the length ofrotating portion 110 a, downwardly toward a distal end of the deploymentmechanism 103. Channel 113 b includes a first portion 113 b 1 that runsdiagonally along the length of the rotating portion 110 a, upwardlytoward a proximal end of the deployment mechanism 103, and a secondportion that is straight and runs perpendicular to the length of therotating portion 110 a. The point at which first portion 113 a 1transitions to second portion 113 a 2 along channel 113 a, is the sameas the point at which first portion 113 b 1 transitions to secondportion 113 b 2 along channel 113 b. Channel 113 c is straight and runsperpendicular to the length of the rotating portion 110 a. Within eachof channels 113 a, 113 b, and 113 c, sit members 114 a, 114 b, and 114 crespectively. Members 114 a, 114 b, and 114 c are movable withinchannels 113 a, 113 b, and 113 c. Members 114 a, 114 b, and 114 c alsoact as stoppers that limit movement of rotating portion 110 a, whichthereby limits axial movement of the shaft 104.

FIG. 21 shows a cross-sectional view of deployment mechanism 103. Member114 a is connected to the proximal portion 109 of the deploymentmechanism 103. Movement of member 114 a results in retraction of theproximal portion 109 of the deployment mechanism 103 to within thedistal portion 110 of the deployment mechanism 103. Member 114 b isconnected to a pusher component 118. The pusher component 118 extendsthrough the proximal portion 109 of the deployment mechanism 103 andextends into a portion of hollow shaft 104. The pusher component isinvolved in deployment of a shunt from the hollow shaft 104. Anexemplary pusher component is a plunger. Movement of member 114 bengages pusher 118 and results in pusher 118 advancing within hollowshaft 104.

Reference is now made to FIGS. 22-24, which accompany the followingdiscussion regarding deployment of a shunt 115 from deployment device100. FIG. 22A shows deployment device 100 is a pre-deploymentconfiguration. In this configuration, shunt 115 is loaded within hollowshaft 104 (FIG. 22C). As shown in FIG. 22C, shunt 115 is only partiallywithin shaft 104, such that a portion of the shunt is exposed. However,the shunt 115 does not extend beyond the end of the shaft 104. In otherembodiments, the shunt 115 is completely disposed within hollow shaft104. The shunt 115 is loaded into hollow shaft 104 such that the shuntabuts pusher component 118 within hollow shaft 104. A distal end ofshaft 104 is beveled to assist in piercing tissue of the eye.

Additionally, in the pre-deployment configuration, a portion of theshaft 104 extends beyond the housing 101 (FIG. 22C). The deploymentmechanism is configured such that member 114 a abuts a proximal end ofthe first portion 113 a 1 of channel 113 a, and member 114 b abut aproximal end of the first portion 113 b 1 of channel 113 b (FIG. 22B).In this configuration, the ready indicator 111 is visible through slot106 of the housing 101, providing feedback to an operator that thedeployment mechanism is in a configuration for deployment of anintraocular shunt from the deployment device 100 (FIG. 22A). In thisconfiguration, the device 100 is ready for insertion into an eye(insertion configuration or pre-deployment configuration). Methods forinserting and implanting shunts are discussed in further detail below.

Once the device has been inserted into the eye and advanced to alocation to where the shunt will be deployed, the shunt 115 may bedeployed from the device 100. The deployment mechanism 103 is atwo-stage system. The first stage is engagement of the pusher component118 and the second stage is retraction of the proximal portion 109 towithin the distal portion 110 of the deployment mechanism 103. Rotationof the rotating portion 110 a of the distal portion 110 of thedeployment mechanism 103 sequentially engages the pusher component andthen the retraction component.

In the first stage of shunt deployment, the pusher component is engagedand the pusher partially deploys the shunt from the deployment device.During the first stage, rotating portion 110 a of the distal portion 110of the deployment mechanism 103 is rotated, resulting in movement ofmembers 114 a and 114 b along first portions 113 a 1 and 113 b 1 inchannels 113 a and 113 b. Since the first portion 113 a 1 of channel 113a is straight and runs perpendicular to the length of the rotatingportion 110 a, rotation of rotating portion 110 a does not cause axialmovement of member 114 a. Without axial movement of member 114 a, thereis no retraction of the proximal portion 109 to within the distalportion 110 of the deployment mechanism 103. Since the first portion 113b 1 of channel 113 b runs diagonally along the length of the rotatingportion 110 a, upwardly toward a proximal end of the deploymentmechanism 103, rotation of rotating portion 110 a causes axial movementof member 114 b toward a proximal end of the device. Axial movement ofmember 114 b toward a proximal end of the device results in forwardadvancement of the pusher component 118 within the hollow shaft 104.Such movement of pusher component 118 results in partially deployment ofthe shunt 115 from the shaft 104.

FIGS. 23A to 23C show schematics of the deployment mechanism at the endof the first stage of deployment of the shunt from the deploymentdevice. As is shown FIG. 23A, members 114 a and 114 b have finishedtraversing along first portions 113 a 1 and 113 b 1 of channels 113 aand 113 b. Additionally, pusher component 118 has advanced within hollowshaft 104 (FIG. 23B), and shunt 115 has been partially deployed from thehollow shaft 104 (FIG. 23C). As is shown in these figures, a portion ofthe shunt 115 extends beyond an end of the shaft 104.

In the second stage of shunt deployment, the retraction component isengaged and the proximal portion of the deployment mechanism isretracted to within the distal portion of the deployment mechanism,thereby completing deployment of the shunt from the deployment device.During the second stage, rotating portion 110 a of the distal portion110 of the deployment mechanism 103 is further rotated, resulting inmovement of members 114 a and 114 b along second portions 113 a 2 and113 b 2 in channels 113 a and 113 b. Since the second portion 113 b 2 ofchannel 113 b is straight and runs perpendicular to the length of therotating portion 110 a, rotation of rotating portion 110 a does notcause axial movement of member 114 b. Without axial movement of member114 b, there is no further advancement of pusher 112. Since the secondportion 113 a 2 of channel 113 a runs diagonally along the length of therotating portion 110 a, downwardly toward a distal end of the deploymentmechanism 103, rotation of rotating portion 110 a causes axial movementof member 114 a toward a distal end of the device. Axial movement ofmember 114 a toward a distal end of the device results in retraction ofthe proximal portion 109 to within the distal portion 110 of thedeployment mechanism 103. Retraction of the proximal portion 109,results in retraction of the hollow shaft 104. Since the shunt 115 abutsthe pusher component 118, the shunt remains stationary at the hollowshaft 104 retracts from around the shunt 115 (FIG. 24C). The shaft 104,retracts almost completely to within the housing 101. During both stagesof the deployment process, the housing 101 remains stationary and in afixed position.

FIG. 24A shows a schematic of the device 100 after deployment of theshunt 115 from the device 100. FIG. 24B shows a schematic of thedeployment mechanism at the end of the second stage of deployment of theshunt from the deployment device. As is shown in FIG. 24B, members 114 aand 114 b have finished traversing along second portions 113 a 1 and 113b 1 of channels 113 a and 113 b. Additionally, proximal portion 109 hasretracted to within distal portion 110, thus resulting in retraction ofthe hollow shaft 104 to within the housing 101. FIG. 24D shows anenlarged view of the distal portion of the deployment device afterdeployment of the shunt. This figure shows that the hollow shaft 104 isnot fully retracted to within the housing 101 of the deployment device100. However, in certain embodiments, the shaft 104 may completelyretract to within the housing 101.

Incorporation by Reference

References and citations to other documents, such as patents, patentapplications, patent publications, journals, books, papers, webcontents, have been made throughout this disclosure. All such documentsare hereby incorporated herein by reference in their entirety for allpurposes.

EQUIVALENTS

The invention may be embodied in other specific forms without departingfrom the spirit or essential characteristics thereof. The foregoingembodiments are therefore to be considered in all respects illustrativerather than limiting on the invention described herein. Scope of theinvention is thus indicated by the appended claims rather than by theforegoing description, and all changes which come within the meaning andrange of equivalency of the claims are therefore intended to be embracedtherein.

1.-19. (canceled)
 20. A method of placing an intraocular shunt into ahuman eye, the method comprising: advancing a hollow shaft through theanterior chamber, the hollow shaft holding the intraocular shunt andhaving a distal tip, the distal tip comprising a bevel; penetrating thesclera with the beveled distal tip until all of the bevel is positioneddistal to a distal wall of the sclera; after all of the bevel has beenpositioned distal to the distal wall, advancing the shunt at leastpartially from the hollow shaft into a space between the sclera andTenon's capsule; and withdrawing the hollow shaft from the eye.
 21. Themethod of claim 20, further comprising advancing the hollow shaftthrough the cornea.
 22. The method of claim 20, wherein furthercomprising injecting an aqueous solution into the eye.
 23. The method ofclaim 22, wherein the aqueous solution is injected below Tenon'scapsule.
 24. The method of claim 20, wherein the method is performedwithout inducing subconjunctival blebbing.
 25. The method of claim 20,wherein the shunt is deployed into the eye without the use of an opticalapparatus.
 26. The method of claim 25, therein the optical apparatus isa goniolens.
 27. The method of claim 20, wherein the shunt is deployedinto the eye with the use of an optical apparatus that does not directlycontact the eye.
 28. The method of claim 27, wherein the opticalapparatus is an ophthalmic microscope.
 29. The method of claim 20,wherein the beveled distal tip comprises three bevels with a first bevelof the three bevels being located proximal to the other bevels, andwherein the sclera is penetrated with the beveled distal tip until anentirety of the first bevel is positioned distal to a distal wall of thesclera.
 30. A method of placing an intraocular shunt into an eyecomprising a cornea, an anterior chamber, a sclera, and a Tenon'scapsule, the method comprising: inserting a hollow shaft from theanterior chamber through the sclera toward Tenon's capsule, the hollowshaft holding the intraocular shunt and having a beveled distal tip andan unbeveled portion proximal to the beveled distal tip; positioning theunbeveled portion distal to a distal wall of the sclera; afterpositioning the unbeveled portion to the distal wall of the sclera,withdrawing the hollow shaft from the eye and leaving a distal end ofthe shunt in a space between the sclera and Tenon's capsule.
 31. Themethod of claim 30, further comprising advancing the hollow shaftthrough the cornea.
 32. The method of claim 30, wherein furthercomprising injecting an aqueous solution into the eye.
 33. The method ofclaim 32, wherein the aqueous solution is injected below Tenon'scapsule.
 34. The method of claim 30, wherein the method is performedwithout inducing subconjunctival blebbing.
 35. The method of claim 30,wherein the shunt is deployed into the eye without the use of an opticalapparatus.
 36. The method of claim 35, wherein the optical apparatus isa goniolens.
 37. The method of claim 30, wherein the shunt is deployedinto the eye with the use of an optical apparatus that does not directlycontact the eye.
 38. The method of claim 37, wherein the opticalapparatus is an ophthalmic microscope.